Despite significant advances in the treatment of depression,
many patients fail to respond to treatment with adequate dose and
duration. Multiple therapeutic approaches are available for the
treatment of patients not responding to standard antidepressant
medication. These include switching medication or combination and
augmentation strategies. A substantial number of patients do not
respond to multiple treatment trials. These patients suffer from
treatment-resistant depression (TRD) and represent a challenge to
the treating physician. There have been a growing number of
reports on the use of atypical antipsychotics as augmenting
agents in nonpsychotic TRD. Second-generation antipsychotics are
less likely to provoke parkinsonian side effects. It has also
been reported that these agents produce lower rates of tardive
movement disorders than traditional neuroleptics. Furthermore,
second-generation antipsychotics are serotonin-2A/2C antagonists,
possibly allowing them to improve the efficacy and some aspects
of the side effect profile of selective serotonin reuptake
inhibitors (SSRIs). Weight gain and sedation are likely to be the
most common adverse events of such combined therapy. In a recent
controlled clinical trial, the atypical antipsychotic olanzapine
was combined with fluoxetine therapy in an 8-week, double-blind
clinical trial in patients with TRD. This combination drug
therapy demonstrated clinical efficacy on several rating scales
and showed rapid onset of action. Although more studies will be
required to confirm and extend these findings, the results
suggest that there may be a clinical benefit to combining
atypical antipsychotics with SSRIs in nonpsychotic TRD.